Abstract
We have developed unique replication-competent retroviral (RCR) vectors based on murine leukemia virus that provide improved efficiency of viral delivery, allow for long-term transgene expression and demonstrate an intrinsic selectivity for transduction of rapidly dividing tumor cells. The purpose of this study was to evaluate the in vivo transduction efficiency and the therapeutic efficacy of the RCR vector mediated delivery of Escherichia coli purine nucleoside phosphorylase (PNP) in combination with fludarabine phosphate for bladder cancer. We constructed vectors containing green fluorescent protein (GFP) gene (ACE)-GFP) or PNP gene (ACE-PNP). KU-19-19 bladder tumors exhibited 28.3±16.1, 46.6±5.8 and 93.7±7.8% of GFP expression on 14, 18 and 26 days after intratumoral injection of ACE-GFP, respectively. GFP expression could not be observed in normal tissues surrounding the injected tumors. No detectable polymerase chain reaction products of GFP gene could be observed in any distant organs. Intratumoral injection of ACE-PNP, followed by systemically administered fludarabine phosphate, significantly inhibited the growth of pre-established KU-19-19 tumors. Our results indicate that RCR vectors are a potentially efficient gene delivery method and that the RCR vector mediated PNP gene transfer and fludarabine phosphate treatment might be a novel and potentially therapeutic modality for bladder cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 279-286 |
| Number of pages | 8 |
| Journal | Cancer Gene Therapy |
| Volume | 14 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2007 Mar |
| Externally published | Yes |
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Keywords
- Fludarabine phosphate
- Purine nucleoside phosphorylase
- Retroviral vector
- Suicide gene
ASJC Scopus subject areas
- Cancer Research
- Genetics
Cite this
Delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts. / Kikuchi, Eiji; Menendez, S.; Ozu, C.; Ohori, M.; Cordon-Cardo, C.; Logg, C. R.; Kasahara, N.; Bochner, B. H.
In: Cancer Gene Therapy, Vol. 14, No. 3, 03.2007, p. 279-286.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts
AU - Kikuchi, Eiji
AU - Menendez, S.
AU - Ozu, C.
AU - Ohori, M.
AU - Cordon-Cardo, C.
AU - Logg, C. R.
AU - Kasahara, N.
AU - Bochner, B. H.
PY - 2007/3
Y1 - 2007/3
N2 - We have developed unique replication-competent retroviral (RCR) vectors based on murine leukemia virus that provide improved efficiency of viral delivery, allow for long-term transgene expression and demonstrate an intrinsic selectivity for transduction of rapidly dividing tumor cells. The purpose of this study was to evaluate the in vivo transduction efficiency and the therapeutic efficacy of the RCR vector mediated delivery of Escherichia coli purine nucleoside phosphorylase (PNP) in combination with fludarabine phosphate for bladder cancer. We constructed vectors containing green fluorescent protein (GFP) gene (ACE)-GFP) or PNP gene (ACE-PNP). KU-19-19 bladder tumors exhibited 28.3±16.1, 46.6±5.8 and 93.7±7.8% of GFP expression on 14, 18 and 26 days after intratumoral injection of ACE-GFP, respectively. GFP expression could not be observed in normal tissues surrounding the injected tumors. No detectable polymerase chain reaction products of GFP gene could be observed in any distant organs. Intratumoral injection of ACE-PNP, followed by systemically administered fludarabine phosphate, significantly inhibited the growth of pre-established KU-19-19 tumors. Our results indicate that RCR vectors are a potentially efficient gene delivery method and that the RCR vector mediated PNP gene transfer and fludarabine phosphate treatment might be a novel and potentially therapeutic modality for bladder cancer.
AB - We have developed unique replication-competent retroviral (RCR) vectors based on murine leukemia virus that provide improved efficiency of viral delivery, allow for long-term transgene expression and demonstrate an intrinsic selectivity for transduction of rapidly dividing tumor cells. The purpose of this study was to evaluate the in vivo transduction efficiency and the therapeutic efficacy of the RCR vector mediated delivery of Escherichia coli purine nucleoside phosphorylase (PNP) in combination with fludarabine phosphate for bladder cancer. We constructed vectors containing green fluorescent protein (GFP) gene (ACE)-GFP) or PNP gene (ACE-PNP). KU-19-19 bladder tumors exhibited 28.3±16.1, 46.6±5.8 and 93.7±7.8% of GFP expression on 14, 18 and 26 days after intratumoral injection of ACE-GFP, respectively. GFP expression could not be observed in normal tissues surrounding the injected tumors. No detectable polymerase chain reaction products of GFP gene could be observed in any distant organs. Intratumoral injection of ACE-PNP, followed by systemically administered fludarabine phosphate, significantly inhibited the growth of pre-established KU-19-19 tumors. Our results indicate that RCR vectors are a potentially efficient gene delivery method and that the RCR vector mediated PNP gene transfer and fludarabine phosphate treatment might be a novel and potentially therapeutic modality for bladder cancer.
KW - Fludarabine phosphate
KW - Purine nucleoside phosphorylase
KW - Retroviral vector
KW - Suicide gene
UR - http://www.scopus.com/inward/record.url?scp=33847043563&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847043563&partnerID=8YFLogxK
U2 - 10.1038/sj.cgt.7701013
DO - 10.1038/sj.cgt.7701013
M3 - Article
VL - 14
SP - 279
EP - 286
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
SN - 0929-1903
IS - 3
ER -